1. Quality of Life after HCT – What can an outcomes registry do?
Douglas Rizzo, MD MS
October 20, 2016

2. CIBMTR Number of Patients Registered, 1970-2015
Updated SK/RD 1/30/14

3. What are the outcomes ?

4. What are the outcomes of HCT?
Overall survival is gradually improving
BUT, there is more to the story ….

5. Number of HCT Survivors Increasing
Estimated ~110,000 HCT survivors in the US in 2009
~5X increase by 2030 if transplant rates stay stable
NS Majhail et al, BBMT 2013

6. Long-term Survival after HCT
Reference
Patients
Overall Survival
CGVHD & Mortality Risk
Life Expectancy
AUTOLOGOUS HCT
Bhatia et al (2007), BMT-SS
N=854, multiple ds
(≥2 yr survivors)
10 yrs --
Same (for select pts)
Majhail et al (2009), CIBMTR
N=1367, lymphoma
Same
ALLOGENEIC HCT
N=1479, multiple ds (≥2 yr survivors)
15 yrs √
15 yrs
Goldman et al (2010), CIBMTR
N=2444, CML
(≥5 yr survivors)
Wingard et al (2011), CIBMTR
N=10632, multiple ds
COMBINED
Martin et al (2010), FHCRC
N=2574, multiple ds
20 yrs
30 yrs

7. Burden of Late Morbidity
Late complications are significant issue for survivors
BMT-SS – 1022 auto and allo HCT 2-year survivors
Cumulative incidence of chronic health conditions
CL Sun et al, Blood 2010 ; 116: 3129

8. Late morbidity after HCT:
Patients report broad array of impairments, including:
Cognitive deficits
Sexual dysfunction
Emotional distress
Fatigue and sleep disturbances
Social engagement
Inability to return to work/disability
Financial difficulties
Significant impact on quality of life

9. Key Question 4:
Are there new measures of quality not currently reported publicly by the CIBMTR which should be included in future iterations of the center-specific survival analysis (with risk adjustment) on behalf of the HCT community?

10. KQ4: New quality measures?
Develop and test a 3 year risk adjusted overall survival measure – pilot for center use
Work in progress: pilot testing underway for 2015 Report (HCT )
Assess feasibility of collecting and reporting Patient Reported Outcomes
QOL pilot analysis in final manuscript phase
Exploring tools by which CIBMTR and centers can collect these data
EMR or PROMIS (NIH)

11. Centralized patient reported quality of life collection in HCT patients is feasible, and higher pre-HCT scores significantly predict better overall survival post-transplant
Bronwen Shaw, MD PHD
Professor of Medicine, MCW Senior Scientific Director, CIBMTR
There are no conflicts of interest to disclose.

12. Background and Aims
Patient Reported Outcomes (PRO) are associated with outcomes after HCT, but are not routinely collected in outcomes registries
Primary Aim:
A pilot project to evaluate the feasibility of prospective collection of PRO at 8 transplant centers reporting clinical data to the CIBMTR
Secondary Aim:
To correlate PRO with clinical and demographic data routinely collected

13. Study Schema

14. Patients and Methods
Standard pre-transplant, treatment variables and clinical outcomes were collected (CIBMTR forms completed by centers)
Additional socio-demographic form at baseline
PRO measures:
Adults: FACT-BMT and SF36
Children/parents: age appropriate and proxy PedsQL modules
A satisfaction survey was completed by participants at 12 months

15. Time point retention Adults Pediatrics Pre-HCT Day 100 6/12 1 year
Total received
295
173
163
136
Total approached
301
238
202
174
Overall retention rate
98.01%
57.48%
54.15%
45.18%
Time point retention rate
72.69%
80.69%
78.16%
Pediatrics
Pre-HCT
Day 100
6/12
1 year
Total received 78 50 43
Total approached 89 85 79 72
Overall retention rate
87.64%
56.18%
48.31%
Time point retention rate
58.82%
63.29%
59.72%

16. Change in QOL over time

17. Factors associated with survival
In adults baseline FACT-BMT and PCS of SF36 were associated with
overall survival and QoL at 1 year
Baseline MCS was not significantly associated with OS
Effects in children are less marked, but follow the same pattern
PRO Score pre-HCT (higher is better)
RR of mortality (95%CI)
p-value
FACT-BMT (adult)
10 point increase
0.83 ( )
0.0003
PCS of SF36 (adult)
0.78 ( )
0.0147
PedsQL (child)
0.69 ( )
0.0444
PedsQL (parent)
0.79 ( )
0.0816

18. Conclusions
Feasible to prospectively collect PRO directly from patients at multiple time points
High enrollment and return rate
Good patient satisfaction and ongoing interest
Baseline PROs are significantly associated with survival and post transplant QoL after adjusting for clinical factors
Routine collection of PRO adds value to current clinical data

19. Why collect PRO?
BMT CTN 0201: RCT of PB v BM for UNR donors

20. How can PRO fill the picture - 0201
5 year follow-up with patient reported data
No difference Relapse, TRM, OS
BM recipients more likely to return to work (OR 1.5; 95% CI )
Lee SJ et al. JAMA Oncology online Aug 2016

21. Other studies where PRO associated with OS: CTN 0902
But: No differences in SF-36 PCS or MCS, or other PRO at day 100 with either exercise or stress reduction interventions
Wood, WA et al. Cancer;122:91-98, 2016

22. NIH BMT Late Effects Consensus Recommendations
Quality of Life and Psychosocial Working Group

23. Outcomes: Recommendations
Research directions:
Integrate assessment of key and understudied outcomes (e.g. depression/distress, physical function, cognitive function, pain syndromes, financial toxicity) into standard and new clinical protocols examining therapies, preparative regimens and cGVHD prophylaxis and treatment.
Implement multicenter longitudinal studies with standardized measures and time points to improve knowledge of high prevalence/impact outcomes in pediatrics and non-malignant conditions (otherwise always small sample sizes) and other understudied populations.

24. Can we leverage the CIBMTR data collection platform to collect PRO more routinely?

25. What can we do in the future?
Explore a direct-to-patient interface to collect PRO from patients and connect those data to robust clinical data regarding their HCT
Use the same “core” PRO measures in all research studies of HCT patients
Consider core and variable measures
Use a system which is free, easy to access (?PROMIS ?)
Ensure a low burden for centers (and patients)
Use a single system of items which is versatile
Flexible, change over time
Shaw, BE et al; Harmonization of HRQOL in HCT; BMT May 2016

26. Vision-Mission: Vision Mission
The Patient-Reported Outcomes Measurement Information System (PROMIS®), funded by the National Institutes of Health, aims to provide clinicians and researchers access to efficient, precise, valid, and responsive adult- and child-reported measures of health.
Mission
PROMIS uses measurement science to create an efficient state-of-the-art assessment system for self-reported health.

27. The PROMIS of a better future…
A publicly available, adaptable and sustainable Internet-based system that will:
Administer individually “tailored” questionnaires (using Computer Adaptive Testing (CAT) technology) to measure health status outcomes
Collect and analyze responses
Provide instant health status reports to users to:
Enhance research
Improve clinical decision-making
Facilitate policy-making by health plan and systems and public programs

28. How will this help?
Standardized, adaptable, longitudinal PRO data collection to:
Characterize the PRO deficits patients experience – including to plan interventions
Utilize patient-reported status as a more accurate and representative measure of patients’ health status in multivariate analyses
Analyze effectiveness of various interventions across broad group of transplant centers
Comparison group for non-randomized interventions

29. High priority questions to address
What role can centers play in data collection?
What is the real purpose for collection of QOL
Research?
Understanding the “holistic” patient experience?
Public reporting?
Do we understand Quality of Life well enough to make it publicly reportable
What are the unintended consequences?
Funding $$$

31. QOL reference slides

32. What is a PRO?
Patient-reported outcomes (PROs) are generally understood to encompass symptoms, functional status, and perceptions of health status or health-related quality of life (HRQoL) as reported directly by the patient without interpretation from clinicians
( accessed 2 July 2015).

33. Patients Selection criteria for analysis Excluded Included
Total number approached to be in study
390
Transplant never occurred 28
Canceled (21)
Deceased (7)
362
Patients withdrew before completing baseline or transplant 6
356
Patients consented to study but did not returned any surveys  5
351
Returned incomplete FACT-BMT baseline measure (not scorable) 4
347
QOL: Patients did not fill out baseline measure 7
340

34. Demographics Adults Pediatrics Gender Male 154 (58) 45 (54) Female
Male
154 (58)
45 (54)
Female
110 (42)
38 (46)
Race
Caucasian
236 (89)
67 (81)
Other
26 (10)
15 (18)
Unknown/declined
2 (<1)
1 (1)
Karnofsky/Lansky performance score
≥90%
158 (60)
73 (88)
<90%
106 (40)
10 (12)
Sorror score
63 (24)
55 (66)
1 -2
93 (35)
19 (22)
= or > 3
101 (37)
7 (8)
Missing
7 (3)
2 (2)
Marital status (adults only)
Married or living with partner
182 (69)
N/A
Single/separated/divorced/widowed
55 (21)
27 (10)
Household income level
< 60,000
52 (20)
36 (43)
≥60,000
78 (30)
29 (35)
134 (50)
18 (22)
Median follow-up of survivors (range), months
26 (8-38)
25 (6-46)

35. Demographics Adults Pediatrics Indication for transplant
Acute leukemia
130 (49)
32 (39)
CML
19 (7)
1 (1)
MDS/MPS
49 (19)
4 (5)
Other leukemia
20 (8)
NHL
22 (8) HD
6 (2)
Multiple myeloma
7 (3)
Non-malignant diseases
11 (4)
46 (55)
Myeloablative conditioning regimen No
125 (47)
23 (28)
Yes
139 (53)
60 (72)
TBI use
150 (57)
53 (64)
114 (43)
30 (36)
Donor
Matched relative
104 (39)
12 (14)
Mismatched relative
4 (2)
Matched URD
105 (40)
51 (61)
Mismatched URD
7 (8)
Cord blood
29 (11)
Year of transplant
2011
25 (9)
9 (11)
2012
185 (70)
55 (66)
2013
54 (20)
19 (23)

36. Baseline QOL scores Adults Pediatrics
Completed baseline QOL survey (FACT-BMT for adults PedsQL for children) No
1 (<1)
6 (7)
Yes
263 (99)
77 (93)
Median (range) Baseline FACT-BMT score
104 (53-148)
N/A
Baseline SF36-PCS (higher is better)
< 50
193 (73)
≥ 50
63 (24)
Missing
8 (3)
Baseline SF36-MCS (higher is better)
118 (45)
138 (52)
Baseline PedsQL self-reported
< 69.7
28 (34)
≥ 69.7
24 (29)
7 (8)
N/A – children under age 5
Baseline PedsQL proxy reported
< 65.4
36 (43)
≥ 65.4
38 (46)
9 (11)

37. Factors associated with feasibility
Adults:
Factors negatively associated with retention were race other than Caucasian (OR 0.21; CI ; p<0.0001) and unmarried status (OR 0.41; CI ; p=0.0002)
Pediatrics:
Higher family income (OR 4.72; CI ; p=0.0005) was positively associated with retention

38. Adjusted OS by FACT baseline quartile

39. Conclusions
Feasible to prospectively collect PRO at multiple time points for unselected transplant patients
High return rate
Good patient satisfaction
Baseline PROs are significantly predictive of survival and post transplant QoL adjusting for clinical factors
Routine PRO adds value to current clinical data collection

40. NIH PROMIS